Abstract More than 300 independent stress reduction programs in medical facilities throughout the US and the world are modeled on either Herbert Benson's Relaxation Response (RR) program or the Mindfulness-Based Stress Reduction (MBSR) program developed by Jon Kabat-Zinn. Although both treatments are based on meditation, the scientific philosophies and meditative traditions upon which each is founded are different and these differences are reflected in the instructions and exercises taught to patients. There is considerable published evidence supporting the efficacy of each program and our preliminary data suggests that each intervention may be associated with differential mechanisms of action. Our functional MRI data suggests that each style of meditation is associated with statistically significant differences in regional activation; furthermore each form of meditation is associated with a differential pattern and magnitude of respiratory change. This is a first-time collaboration with the founding institutions of each intervention and the Martinos Center for Biomedical Imaging at the MGH. In this pilot study, functional MRI will be combined with behavioral measures for determining the depth of the relaxation response and changes in mindfulness to evaluate specific neurological, physiological and psychological outcomes of the RR and MBSR interventions. The data gained from these studies will provide the first direct evidence of differential mechanisms of action between these two popular stress reduction interventions. These aims are in accordance with NCCAM's stated research priority for the funding of studies geared to elucidating mechanisms of action underlying efficacious complementary and alternative medical practices. We will conduct a clinical trial of 60 adults with self-reported sub-clinical psychological distress. Subjects will be randomized to receiving the RR (n=30) or MBSR (n=30) program. Before and after recieveing one of the interventions, all subjects will attend data collection sessions in the GCRC and MRI scanner, and complete psychological questionnaires. Maintenance of clinical outcome will be assessed at the three-month follow-up timepoint.